rs13331

Variant names:

• chr17-7190147-A-G
• rs13331
• ENST00000489885.1:n.1637T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000489885.1(DLG4):​n.1637T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 149,298 control chromosomes in the GnomAD database, including 38,526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (38488 hom., cov: 24)
  • Exomes 𝑓: 0.54 (38 hom.)
• Consequence: DLG4 ENST00000489885.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 18 publications found

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLG4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder 62

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000489885.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NM_001365.5	MANE Plus Clinical	c.*561T>C		3_prime_UTR	Exon 22 of 22	NP_001356.1
	DLG4	NM_001321075.3	MANE Select	c.*561T>C		3_prime_UTR	Exon 20 of 20	NP_001308004.1
	DLG4	NR_135527.1		n.3956T>C		non_coding_transcript_exon	Exon 21 of 21

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000489885.1	TSL:1	n.1637T>C		non_coding_transcript_exon	Exon 2 of 2
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.*561T>C		3_prime_UTR	Exon 22 of 22	ENSP00000497806.3
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.*561T>C		3_prime_UTR	Exon 20 of 20	ENSP00000382425.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 105947 AN: 148938 Hom.: 38432 Cov.: 24

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.536 AC: 135 AN: 252 Hom.: 38 Cov.: 0 AF XY: 0.567 AC XY: 76 AN XY: 134

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.526 AC: 20 AN: 38

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.700 AC: 7 AN: 10

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.526 AC: 103 AN: 196

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.712 AC: 106055 AN: 149046 Hom.: 38488 Cov.: 24 AF XY: 0.711 AC XY: 51621 AN XY: 72554

African (AFR) AF: 0.852 AC: 34093 AN: 40036

American (AMR) AF: 0.611 AC: 9178 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2227 AN: 3454

East Asian (EAS) AF: 0.626 AC: 3144 AN: 5026

South Asian (SAS) AF: 0.683 AC: 3242 AN: 4748

European-Finnish (FIN) AF: 0.725 AC: 7099 AN: 9794

Middle Eastern (MID) AF: 0.795 AC: 229 AN: 288

European-Non Finnish (NFE) AF: 0.661 AC: 44786 AN: 67708

Other (OTH) AF: 0.710 AC: 1463 AN: 2062

Alfa AF: 0.675 Hom.: 29300

Bravo AF: 0.708

Asia WGS AF: 0.695 AC: 2417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13331; hg19: chr17-7093466;